title: Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice.
abstract: Stable integration of HIV proviral DNA into host cell chromosomes, a hallmark and essential feature of the retroviral life cycle, establishes the infection permanently. Current antiretroviral combination drug therapy cannot cure HIV infection. However, expressing an engineered HIV-1 long terminal repeat (LTR) site-specific recombinase (Tre), shown to excise integrated proviral DNA in vitro, may provide a novel and highly promising antiviral strategy. We report here the conditional expression of Tre-recombinase from an advanced lentiviral self-inactivation (SIN) vector in HIV-infected cells. We demonstrate faithful transgene expression, resulting in accurate provirus excision in the absence of cytopathic effects. Moreover, pronounced Tre-mediated antiviral effects are demonstrated in vivo, particularly in humanized Rag2⁻/⁻γc⁻/⁻ mice engrafted with either Tre-transduced primary CD4⁺ T cells, or Tre-transduced CD34⁺ hematopoietic stem and progenitor cells (HSC). Taken together, our data support the use of Tre-recombinase in novel therapy strategies aiming to provide a cure for HIV.
authors.affiliation: Heinrich Pette Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Ilona
authors.initials: I
authors.lastname: Hauber
authors.forename: Helga
authors.initials: H
authors.lastname: Hofmann-Sieber
authors.forename: Jan
authors.initials: J
authors.lastname: Chemnitz
authors.forename: Danilo
authors.initials: D
authors.lastname: Dubrau
authors.forename: Janet
authors.initials: J
authors.lastname: Chusainow
authors.forename: Rolf
authors.initials: R
authors.lastname: Stucka
authors.forename: Philip
authors.initials: P
authors.lastname: Hartjen
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.forename: Patrick
authors.initials: P
authors.lastname: Ziegler
authors.forename: Karl
authors.initials: K
authors.lastname: Hackmann
authors.forename: Evelin
authors.initials: E
authors.lastname: Schröck
authors.forename: Udo
authors.initials: U
authors.lastname: Schumacher
authors.forename: Christoph
authors.initials: C
authors.lastname: Lindner
authors.forename: Adam
authors.initials: A
authors.lastname: Grundhoff
authors.forename: Christopher
authors.initials: C
authors.lastname: Baum
authors.forename: Markus G
authors.initials: MG
authors.lastname: Manz
authors.forename: Frank
authors.initials: F
authors.lastname: Buchholz
authors.forename: Joachim
authors.initials: J
authors.lastname: Hauber
mesh_terms: D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011533:Proviruses / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic; D018183:Transplantation Chimera; D016662:Virus Integration / Q000235:genetics
chemical_list: D019426:Integrases; C583669:Tre-Recombinase